High-resolution in vivo imaging of tissue microstructure can potentially improve the diagnosis and management of many diseases. Several techniques aimed at enabling high-resolution in vivo microscopy are under development in laboratory and pre-clinical studies, including confocal microscopy, optical coherence tomography, and multiphoton microscopy. To be clinically useful, these techniques all aim to comprehensively image an entire 3-dimensional volume of tissue; however, none can capture a full 3-D image dataset in a single acquisition event. All require either mechanical scanning of a focused illumination beam across the sample, or scanning of the illumination wavelength, which slows data acquisition, limits sensitivity, increases system cost and complexity, and reduces image quality through the presence of motion artifacts. Here, we propose a method that for the first time will enable high-resolution snapshot 3-D optical imaging, without the requirement for scanning in any spatial dimension or wavelength. The method, which we term Image Mapped Optical Coherence Tomography (IM-OCT) has become possible by the emergence of three enabling technologies, two of which we have been directly involved with: (1) Hyperspectral imaging by image- mapping spectrometry, (2) Fourier-domain OCT, and (3) the availability of high-sensitivity, high-speed CCD and CMOS array detectors. Our long-term hypothesis is that this approach will significantly advance clinicians' ability to perform in situ evaluation of tissue microstructure. Within this R21 project, we aim to carry out the technical development and preliminary testing to establish the capabilities of IM-OCT imaging in biological tissues. In Aim 1, we will design, assemble, and test a prototype snapshot IM-OCT system. This will include in-house fabrication of a key component - an image mapping mirror comprising multiple angled reflected facets. In Aim 2, we will thoroughly test and evaluate the optical and imaging performance of IM-OCT. We will use our precision microfabrication facilities to produce 3-D test objects, to characterize the optical performance of our imaging platform. The test and evaluation process will then continue through a series of increasingly complex biological imaging experiments, from in vitro tissue phantom studies, to a pilot study with ex vivo human tissue specimens. PUBLIC HEALTH RELEVANCE: High-resolution, instantaneous imaging of tissue microstructure has the potential to aid clinicians in diagnosis and management of many conditions, including cancer, cardiovascular, and retinal diseases. Here, we propose a method that for the first time will provide high-resolution 3-D images of tissue, by acquiring full volumetric image data in a single camera frame capture. We anticipate that this capability will improve the yield of biopsy collection in screening situations, and provide diagnostic information at locations where tissue could not otherwise be removed.